A contra-steric chemoselective hydrometallation strategy with bulky NHC for catalytic asymmetric branched allylamine synthesis

Abstract Development of contra-steric alkene hydrometallation method is one of the keys in branched product synthesis, especially when a bulky ligand steric environment is essential at other stages of the catalytic cycle. This study presents our efforts in this regard with broad scope using N-hetero...

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Bibliographic Details
Main Authors: Weihao Chen, Zhifeng Zhang, Chun-Yu Ho
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60932-w
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Summary:Abstract Development of contra-steric alkene hydrometallation method is one of the keys in branched product synthesis, especially when a bulky ligand steric environment is essential at other stages of the catalytic cycle. This study presents our efforts in this regard with broad scope using N-heterocyclic carbene (NHC), and establishes a chiral (NHC)Ni(II)-catalyzed intermolecular cross-hydroalkenylation system of enamine (alkenyl-carbamate/phthalimide) and α-olefin for the synthesis of highly substituted branched allylamines. A sterically adaptable chiral NHC-Ni(II) catalyst design with an open quadrant enhances interaction with the heteroatom on enamine, offering a precise chemo-, regio-, and enantioselective insertion control throughout the process in a mixture of olefins and allowing convergent synthesis. Besides, α-olefin serves as both terminal and internal 2-alkenyl reagents, yielding a 1,2,3-substituted allylamine by regio- and E-selective isomerization of the 1,2-disubstituted allylamine. Overall, the success of this alkene-based strategy addresses the intrinsic problems associated with alkyne- and alkenyl halide reagent-based synthesis, demonstrates good versatility and scope, and addresses the shortcomings of conceivable approaches based on rigid and sterically bulky NHCs.
ISSN:2041-1723